Intestinal injury in paracetamol overdose (ATOM‐8)

Author:

Perananthan Varan12ORCID,Shihana Fathima12,Chiew Angela L234ORCID,George Jacob5,Dawson Andrew124,Buckley Nicholas A124

Affiliation:

1. Edith Collins Centre Royal Prince Alfred Hospital Sydney New South Wales Australia

2. Clinical Pharmacology and Toxicology Research Group, Biomedical Informatics and Digital Health, Sydney Medical School The University of Sydney Sydney New South Wales Australia

3. Emergency Department and Clinical Toxicology Prince of Wales Hospital and Community Health Services Sydney New South Wales Australia

4. NSW Poisons Information Centre Children's Hospital at Westmead Sydney New South Wales Australia

5. Storr Liver Centre, Westmead Institute for Medical Research Westmead Hospital Sydney New South Wales Australia

Abstract

AbstractBackground and AimParacetamol, a widely used medication, is known for its delayed hepatotoxicity in cases of overdose. However, the potential for intestinal toxicity resulting from very high paracetamol concentrations during absorption is not well explored. This study aims to investigate the presence of intestinal toxicity and its correlation with observations in early and late paracetamol toxicity.MethodsSerial samples of 30 patients with acute paracetamol overdose (> 10 g or 200 mg/kg) were prospectively tested. Markers of enterocyte damage, including plasma intestinal fatty acid binding protein (IFABP) and selected gut‐related microRNAs (miR‐21, miR‐122, miR‐194, and miR‐215), were analyzed. Sub‐analysis was performed on patients presenting with hyperlactatemia defined as a lactate greater than 2 mmol/L within 12 h post ingestion.ResultsIn paracetamol overdose patients, median plasma IFABP was significantly elevated compared with healthy controls (720 μg/L [interquartile range, IQR, 533–1644] vs 270 μg/L [IQR 153–558], P < 0.001). Four patients had early hyperlactatemia and had significantly higher median plasma IFABP compared with those without early hyperlactatemia (3028 μg/L [IQR 1399–3556] vs 574 μg/L [IQR 526–943], P = 0.007). Furthermore, two microRNAs (miR‐122 and miR‐215) were downregulated in early hyperlactatemia (P = 0.019 and P = 0.006, respectively). Plasma IFABP concentrations correlated with paracetamol concentration (Spearman's r = 0.55) and lactate (r = 0.60).ConclusionsParacetamol overdose causes concentration‐related intestinal toxicity, and this is a possible explanation for the early hyperlactatemia syndrome. Intestinal toxicity has potential impacts on pharmacokinetics of other agents ingested and on the evolution of hepatotoxicity. Further studies are required to explore the mechanisms and prognostic implications of intestinal toxicity.

Publisher

Wiley

Subject

Gastroenterology,Hepatology

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